Serum endocan as a predictive biomarker of cardiovascular risk in obese pediatric patients.

BACKGROUND: Endocan is a soluble dermatan sulfate proteoglycan (50 kDa) secreted by endothelial cells and expressed by dermal, coronary, pulmonary and adipose tissue microvasculature. It plays an important role in the pathogenesis of vascular disorders, inflammatory state, endothelium dysfunction and neoangiogenesis. Aims of the study were to compare fasting serum endocan levels between children with obesity and healthy controls and to investigate the relationships between endocan, body mass index (BMI) and other indices of cardiometabolic risk. METHODS: This single-center, observational, retrospective study included 19 pediatric patients with obesity aged 11.94 ± 0.52 years and 19 lean matched controls. Each patient underwent clinical and auxological examination and laboratory investigations including routine organs function tests and lipid profile. Homeostasis model assessment of insulin resistance (HOMA-IR) was calculated. Fasting endocan serum levels were measured using an enzyme-linked immunosorbent assay (ELISA). RESULTS: Compared to healthy subjects, serum endocan levels were found to be significantly upraised in children with obesity. Endocan resulted significantly correlated with insulin levels (rho 0.47; p = 0.04); in addition, an association with HOMA-IR values with a trend toward the statistical significance (rho 0.43; p = 0.07) was found. No significant correlation with fasting blood glucose values and lipid serum levels was demonstrated. Although not statistically significant, a correlation between endocan and the presence and grading of liver steatosis on ultrasound (rho 0.51; p = 0.08 and rho 0.51; p = 0.08, respectively) was found. CONCLUSIONS: These findings confirm the association between endothelial damage and insulin resistance in children with obesity. Endocan could be used as a biomarker of early endothelial dysfunction in children with obesity and could be a valid predictor of future cardiovascular risk in adulthood.

Central and peripheral sensitivity to thyroid hormones and glucose metabolism in prepubertal children with obesity: pilot multicenter evaluation.

PURPOSE: An alteration of central and peripheral sensitivity to thyroid hormones (THs) seems to be associated with an increased risk of prediabetes in adulthood. Aims of this study was to evaluate the relationship between the sensitivity to THs, the severity of overweight and the glyco-metabolic alterations in prepubertal euthyroid children with obesity. METHODS: Prepubertal subjects with simple obesity and matched controls were recruited from three Italian pediatric endocrinology centers and underwent clinical and biochemical evaluations. HOMA-IR, HOMA-ß, insulinogenic index, Matsuda index were evaluated in children with obesity. Indexes of peripheral sensitivity (FT3/FT4 ratio) and central sensitivity (TSH index, TSHI; TSH T4 resistance index, TT4RI; Thyroid Feedback Quantile-based Index, TFQI; Parametric TFQI, PTFQI) to thyroid hormones were calculated in both groups. RESULTS: Eighty prepubertal children with obesity (Group 1; mean age 7.60 ± 1.51 years) and 28 healthy normal-weight controls (Group 2) were recruited. BMI and leptin were higher in group 1 than in group 2. The FT3/FT4 ratio correlated negatively with HOMA-ß (r = -0.29; p = 0.01) and was significantly positively associated with BMI (p = 0.03), IR (p = 0.03) and fasting blood glucose (p = 0.04) in group 1. TT4RI, TSHI, PTFQI, TFQI, were significantly negatively associated with Matsuda-index, IGI and BMI in group 1. CONCLUSION: Central and peripheral sensitivity to thyroid hormones is significantly affected by the severity of overweight and the presence of IR. Altered tissue sensitivity to THs in the prepubertal children with obesity could be implicated in the pathogenesis of glucose metabolism impairment.

Impact of Covid-19 Pandemic on the Effectiveness of Outpatient Counseling in Childhood Obesity Management.

The Covid-19 pandemic drastically modified social life and lifestyle, in particular, among children and adolescents, promoting sedentary behaviors and unhealthy eating habits. The aims of this study were to assess the rate and the factors associated with outpatient drop-out in childhood obesity management, and to evaluate how the Covid-19 pandemic influenced weight status and lifestyle of children and adolescents with obesity. One hundred and forty-five children and adolescents with obesity were identified, including 80 subjects evaluated before the Covid-19 pandemic (group A) and 65 subjects in the period straddling the Covid-19 pandemic (group B). Anamnestic (family history of obesity, dietary habits, physical activity, screen time), socio-cultural (economic status, employment and schooling of parents, household composition, place of living) and clinical (weight, height, BMI, waist circumference) data were retrospectively analyzed for each subject in both groups at baseline (V0) and 12-months (V1) at in-person assessment. Glycemic and lipid profiles were assessed at V0. Drop-out rate did not differ significantly between the two groups. BMI SDS at V0 (OR=2.52; p=0.004), female sex (OR=0.41; p=0.035), and the presence of a single parent in the household (OR=5.74; p=0.033) significantly influenced drop-out in both groups. Weight loss between V0 and V1 was significantly greater among group A patients compared to group B (p=0.031). In group B, hours spent in physical activity significantly decreased from V0 to V1, being significantly lower than group A at V1; on the contrary, screen time significantly increased in the same period. The consumption of sugary drinks and snacks was significantly greater in group B than group A at V1. Our study documented that the Covid-19 pandemic, although not affecting the drop-out rate of obese children in a follow-up program, negatively influenced lifestyle and reduced the effectiveness of outpatient counseling in childhood obesity treatment.

Prospective assessment of liver stiffness by shear wave elastography in childhood obesity: a pilot study.

PURPOSE: The increased incidence of childhood obesity and related non-alcoholic fatty liver disease (NAFLD) has determined the need to identify a non-invasive technique to diagnose and monitor NAFLD. Two-dimensional shear wave elastography (2D-SWE) has emerged as a reliable, non-invasive, tool to evaluate liver tissue elasticity in clinical practice. Aims of this study were to longitudinally evaluate 2D-SWE changes in relation to weight loss, metabolic profile, and body composition modifications and to investigate the correlation between 2D-SWE variation and clinical and biochemical indices of cardio-metabolic risk in obese children. METHODS: Thirty-three children underwent anthropometric, bioimpedenziometric, fasting biochemical assessments, ultrasound, and SWE evaluations, at baseline (V0) and after a 12-months of follow-up (V12). Diet and physical activity programs have been prescribed to all patients according to European Society of Endocrinology and Pediatric Endocrine Society recommendations. Adherence to the prescribed diet and physical activity program was checked every 3 months during the 12-month of follow-up. Variation of all parameters was evaluated in intragroup and intergroup comparison analysis in children, who had not lost weight (Group A) and those who had lost weight (Group B) at V12. Study population was also analyzed dividing it into two groups with respect to 2D-SWE liver elasticity value ≤10.6 kPa or >10.6 kPa. RESULTS: A significant reduction of mean 2D-SWE value was demonstrated both in the entire cohort (p = 0.002) and in Group B children (p = 0.004). Intragroup comparison analysis, between V0 and V12, documented a significant decrease of 2D-SWE and BMI SDS and a significant improvement of metabolic profile (decrease of HOMA-IR, HbA1c, oral glucose tolerance test 120-min glucose and insulin, triglycerides, triglycerides/HDL-ratio, transaminases, uric acid, and increase of Matsuda-index and HDL) in children of Group B but not in those of Group A. Intergroup comparison analysis showed significant differences for BMI, BMI SDS, transaminases and several parameters of glucose and lipid metabolism, between Group A and Group B children after 12-months of follow-up. No significant differences were documented with regard to clinical and biochemical variables by dividing the population in accordance with the 2D-SWE cut-off of 10.6 kPa. CONCLUSIONS: These results suggested a relation between weight loss, metabolic profile improvement and 2D-SWE value reduction. SWE could play a significant role in the non-invasive assessment of NAFLD in children and adolescents with obesity.

The metabolic syndrome in pediatrics: do we have a reliable definition? A systematic review.

OBJECTIVE: Metabolic syndrome is a cluster of cardio-metabolic risk factors associated with an increased risk of cardiovascular disease and type 2 diabetes. In the last two decades, several definitions of metabolic syndrome have been proposed for the pediatric population; all of them agree on the defining components but differ in the suggested criteria for diagnosis. This review aims to analyze the current diagnostic criteria of metabolic syndrome in pediatrics with reference to their feasibility and reliability in clinical practice. METHODS: The systematic research was conducted from January 2003 to June 2020 through MEDLINE via PubMed, Cochrane Library and EMBASE databases. RESULTS: After the selection phase, a total of 15 studies (182 screened) met the inclusion criteria and are reported in the present review. Twelve studies were cross-sectional, two were longitudinal and one was a consensus report. The sample population consisted of multiethnic group or single ethnic group, including Turkish, European, Asian and Hispanic subjects. CONCLUSIONS: To date, there is not a univocal, internationally accepted pediatric definition of metabolic syndrome, which guarantees a high sensitivity and stability of the diagnosis. The definition proposed by IDF results the most straightforward and easy to use in clinical practice, having the unquestionable advantage of requiring measurements quickly accessible in clinical practice, without the adoption of multiple reference tables. Further research is needed to validate a new version of such definition which includes the diagnostic cut-off points recently suggested by published guidelines.

Meal-Related Asprosin Serum Levels Are Affected by Insulin Resistance and Impaired Fasting Glucose in Children With Obesity.

Asprosin physiologically increases in fasting conditions and decreases with refeeding and has been implicated in glucose homeostasis. An alteration of meal-related circadian oscillation of asprosin has been suggested in adults affected by type 2 diabetes mellitus. Aims of this study were to test the hypothesis of an alteration in the meal-related variation of asprosin levels in non-diabetic children and adolescents with obesity and to assess which metabolic variables condition this variation in non-diabetic children and adolescents with obesity. This is a cross-sectional study which included 79 children and adolescents with obesity. Children underwent clinical and biochemical assessments, including oral glucose tolerance test (OGTT), and liver ultrasound evaluation. Asprosin serum levels were measured by an enzyme-linked immunosorbent assay at a fasting state and at the 120-minute OGTT timepoint (2h-postprandial asprosin). Fasting and 2h-postprandial asprosin serum levels did not significantly differ in the entire study population (374.28 ± 77.23 vs 375.27 ± 81.26;p=0.837). 55.7% of patients had a significant increase in 2h-postprandial asprosin compared with fasting levels. The asprosin level increase condition was significantly associated with HOMA-IR (OR,1.41; 95%CI,1.005-1.977; p=0.047), fasting glycaemia (OR,1.073; 95%CI,1.009-1.141;p=0.024) and HOMA-B (OR,0.99; 95%CI,0.984-0.999; p=0.035). Moreover, the IFG condition was associated with the increase in asprosin levels (OR, 3.040; 95%CI, 1.095-8.436; p=0.033), even after adjustment for HOMA-IR, BMI SDS, sex and pubertal stage. Insulin resistance and IFG influence meal-related changes of asprosin serum levels in our study population of obese, non-diabetic, children. Alteration of asprosin circadian secretion might be an early biomarker of impaired glucose regulation in obese children with insulin resistance.